Phosphoramidic acid, ion(2-) → (2S)-((S)-1-phenylethyl) 2-((((2S,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-4-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphorylamino)propanoate

HRID 409014Notes

Reaction equation

HRID 409014 reaction equation
P(N)(=O)([O-])[O-].[NH2:6][C:7]1[N:15]=[C:14]2[C:10]([N:11]=[CH:12][N:13]2[CH:16]2[C@:20]([CH3:22])([OH:21])[CH2:19][C@@H:18]([CH2:23][OH:24])[O:17]2)=[C:9]([O:25][CH3:26])[N:8]=1.C([Mg]Cl)(C)(C)C.Cl[C:34]1[CH:43]=[CH:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35]=1[O:44][P:45](=[N:47][C@@H:48]([CH3:60])[C:49]([O:51][C@H:52]([C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[CH3:53])=[O:50])=[O:46]>C1COCC1>[NH2:6][C:7]1[N:15]=[C:14]2[C:10]([N:11]=[CH:12][N:13]2[CH:16]2[O:17][C@H:18]([CH2:23][O:24][C:34]3[CH:43]=[CH:42][C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:35]=3[O:44][P:45](=[N:47][C@@H:48]([CH3:60])[C:49]([O:51][C@H:52]([C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=3)[CH3:53])=[O:50])=[O:46])[CH2:19][C@:20]2([OH:21])[CH3:22])=[C:9]([O:25][CH3:26])[N:8]=1

Participants

6

Reactant 4

HCID 211207Phosphoramidic acid, ion(2-)HCID 66778689(2S)-((S)-1-phenylethyl) 2-(chloro(naphthalen-1-yloxy)phosphorylamino)propanoateHCID 66778804(3R,5S)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3-olHCID 178418310HCID 178418310, compound

Product 1

HCID 66779897(2S)-((S)-1-phenylethyl) 2-((((2S,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-4-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphorylamino)propanoateYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Using the general procedure for the synthesis of nucleoside 5′-phosphoramidates (Method A), to a solution of (3R,5S)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3-ol 93 mg (0.315 mmol) in 5 mL of THF was added tert-BuMgCl 0.63 mL (0.63 mmol) followed by (2S)-((S)-1-phenylethyl) 2-(chloro(naphthalen-1-yloxy)phosphorylamino)propanoate 282 mg (0.63 mmol) in 5 mL of THF. After work up and silica gel column chromatography, 40 mg of (2S)-((S)-1-phenylethyl) 2-((((2S,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-4-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphorylamino)propanoate was obtained in a 19% yield, as an off-white solid. MS (ES+) m/e: 677.25 (MH+, 100%); Accurate mass: C33H38N6O8P calculated: 677.2489. found 677.2511.

Sources & evidence

ORD record
ord-df9581c2351c488d9e41bd7c6b4f2305
Source dataset
uspto-grants-2014_06
Patent number
US08759318B2

Reaction notes

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